Chromium containing compositions for improving health and fitness

ABSTRACT

Administration of certain chromium complexes in combination with a starch provide unexpected benefits regarding increasing amino acid absorption, protein synthesis, exercise tolerance, lean muscle mass, skeletal muscle hypertrophy, muscle power, muscle endurance, muscle strength, FSR, and decreasing delayed onset muscle soreness, muscle protein breakdown, and fat mass.

INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

This Application is a Divisional of U.S. application Ser. No. 15/427,471filed on Feb. 8, 2017, which claims the benefit of U.S. ProvisionalApplication 62/285,014 filed on Feb. 11, 2016. The entire contents ofthese applications are incorporated herein by reference in theirentirety.

FIELD

The present disclosure relates to compositions for use by those engagingin exercise training, both in elite and amateur athletes, as well as inexercise naïve individuals.

BACKGROUND

Embodiments relate to compositions that comprise, consist essentiallyof, or consist of a chromium complex and a starch for improving musclehealth. In some aspects, the composition includes a chromium picolinatecomplex, a chromium histidinate complex and amylopectin. In someaspects, the composition includes a chromium-amylopectin complex. Insome aspects, the composition also includes at least one amino acidsource. The amino acid source may comprise amino acids that areessential for muscle growth. The amino acids may include one or more ofhistidine, isoleucine, leucine, lysine, methionine, phenylalanine,threonine, tryptophan, and valine. Other embodiments relate to the useof such compositions. These compositions are useful for, inter alia,increasing amino acid absorption, increasing protein synthesis,increasing exercise tolerance, increasing lean muscle mass, increasingskeletal muscle hypertrophy, increasing muscle power, increasing muscleendurance, increasing muscle strength, increasing muscle fractionalsynthesis rate (FSR), decreasing delayed onset muscle soreness,decreasing muscle protein breakdown, and/or decreasing fat mass. In someembodiments, the compositions may be useful for treating or preventingsarcopenia. In some aspects the chromium source is one or more chromiumcomplexes.

Protein Transport and Exercise

Muscles are composed of the contractile proteins myosin and actin, whichtogether form the myofibrils. Contraction occurs when actin ratchetsover myosin, shortening the length of myofibrils. Physical activity isnecessary to maintain normal muscle mass and strength and prevent muscleatrophy. Resistance training results in increased skeletal muscle size(hypertrophy), strength, and endurance, as a biological adaptation toaddressing the increased workload. This adaptation results from changesin the rates of protein synthesis and/or breakdown during and afterresistance training. Such adaptation requires increased amino acidavailability, both to prevent excess muscle tissue breakdown and tofacilitate protein synthesis.

This system requires adequate nutrition to provide the amino acids thatform the protein, but beyond that, the pathways are controlled byactivating factors. Meeting the increased demand for amino acidspost-exertion allows the protein synthesis machinery to be up-regulated,thus allowing for maintenance and/or growth of muscle mass.

Protein intake provides a muscle protein synthesis dose-response up to atotal dose of approximately 20 grams of protein. Protein intake inexcess of the 20 gram ceiling does not result in increased muscleprotein synthesis, and can be harmful, for example, by stimulating aminoacid oxidation. Moore et al., Am. J. Clin. Nutr., vol. 89, pp. 161-168(2009).

Glucose Transport and Exercise

Exercise training may have many effects on skeletal muscle, includingincreased glucose transport. For a short period after exercise, skeletalmuscle glucose transport is insulin-independent. Subsequently, as theacute effect of exercise on glucose transport wears off, skeletalmuscles experience a substantial increase in the sensitivity of theglucose transport process to stimulation by insulin and other activatorsof glucose transport.

Post-Exercise Recovery

Effective post exercise recovery is essential for amateur and eliteathletes to maintain performance, and for individuals new to exercise toderive the most benefit from exercise training and continue with theirexercise regimen. Delayed onset muscle soreness (DOMS) is a familiarexperience for the elite or novice athlete. Symptoms can range frommuscle tenderness to severe debilitating pain. DOMS is most prevalent atthe beginning of the sporting season when athletes are returning totraining following a period of reduced activity. DOMS is also commonwhen athletes are first introduced to certain types of activitiesregardless of the time of year. Resistance exercise induces micro-injuryat a greater frequency and severity than other types of muscle actions.Proper recovery both from a general exercise regime, as well as fromintense training regimes and DOMS requires replenishing muscle glycogenstores, rehydration, and protein supplementation to maintain and/orincrease lean body mass.

Metabolism

During growth, pregnancy, and muscle development, metabolism isprimarily in the anabolic phase, that is, more muscle is added than isbroken down. In contrast, the catabolic phase of muscle growth anddevelopment results in a net loss of lean muscle. This can occur throughboth overtraining, and lack of proper nutrition.

The anabolic/catabolic balance is an important factor not only inhealthy mammals during growth and development but also in disease anddisease management. Muscle wasting in patients with restricted movementis common clinical issue. For example, patients in intensive care oftenbecome catabolic quickly after admission. Similarly, astronauts becomecatabolic in weightless environment of space and begin losing muscletissue and strength almost immediately. Extreme loss of muscle tissueleads to a condition termed cachexia, which is often seen in cancer,trauma, and burn patients. A shift toward catabolism also occurs as anormal part of aging.

Individuals of all ages and athletic abilities can benefit from enhancedmuscle development, i.e., prolonging the anabolic phase. However,methods such as anabolic steroids are not healthy or safe for mostindividuals. Rather, using in weight and/or cardiovascular trainingintense enough to reach the anaerobic threshold, results in a constantflux of tearing down muscle fibers (catabolism) and rebuilding thefibers (anabolism). This cycle of rebuilding is especially rapid duringthe 90 minutes following exercise (the “anabolic window”).

The Role of Chromium

Dietary supplementation of chromium to normal individuals has beenreported to lead to improvements in glucose tolerance, serum lipidconcentrations, including high-density lipoprotein cholesterol, insulinand insulin binding. Anderson, 1986 Clin. Psychol. Biochem. 4:31-41.Supplemental chromium in the trivalent form, e.g. chromic chloride, isassociated with improvements of risk factors associated with adult-onset(Type 2) diabetes and cardiovascular disease.

Chromium is a nutritionally essential trace element. The necessity ofdietary chromium was established in 1959 by Schwartz. Schwartz, “PresentKnowledge in Nutrition,” page 571, fifth edition (1984, the NutritionFoundation, Washington, DC). Chromium depletion is characterized by thedisturbance of glucose, lipid and protein metabolism and by a shortenedlifespan. Chromium is essential for optimal insulin activity in allknown insulin-dependent systems. Boyle et al., 1977 Southern Med. J.70:1449-1453. Insufficient dietary chromium has been linked to bothmaturity-onset diabetes and to cardiovascular disease.

The principal energy sources for the body are glucose and fatty acids.Chromium depletion results in biologically ineffective insulin andcompromised glucose metabolism. Under these conditions, the body reliesprimarily upon lipid metabolism to meet its energy requirements, whichcan lead to the production of elevated amounts of acetyl-CoA and ketonebodies. In some cases, some of the acetyl-CoA can be diverted toincreased cholesterol biosynthesis, resulting in hypercholesterolemia.As such, glycosuria, hypercholesterolemia, and often ketoacidosis areoften associated with diabetes mellitus. The accelerated atheroscleroticprocess seen in diabetics is associated with hypercholesterolemia Boyleet al., supra.

Chromium functions as a cofactor for insulin. It binds to the insulinreceptor and potentiates many, and perhaps all, of its functions. Boyleet al., supra. These functions include, but are not limited to, theregulation of carbohydrate and lipid metabolism. Present Knowledge inNutrition, supra, at p. 573-577. The introduction of inorganic chromiumcompounds per se into individuals is not particularly beneficial.Chromium must be converted endogenously into an organic complex or mustbe consumed as a biologically active molecule. Only about 0.5% ofingested inorganic chromium, however, is assimilated into the body. Only1-2% of most organic chromium compounds are assimilated into the body.Recommended Daily Allowances, Ninth Revised Edition, The NationalAcademy of Sciences, page 160, 1980.

Metal coordination complexes of picolinic acid (pyridine-2-carboxylicacid) have the following structural formula:

wherein M represents the metallic cation and n is equal to the cation'svalence. For example, when M is Cr and n=3, then the compound is chromictripicolinate. Other chromium picolinates include chromic monopicolinateand chromic dipicolinate. The U.S. Recommended Daily Intake (RDI) ofchromium is 120 μg.

U.S. Pat. Nos. 5,087,623; 5,087,624; and 5,175,156, disclose the use ofchromium tripicolinate for supplementing dietary chromium, reducinghyperglycemia and stabilizing serum glucose, increasing lean body massand reducing body fat, and controlling serum lipid levels, including thelowering of undesirably high serum LDL-cholesterol levels and theraising of serum High Density Lipid (HDL)-cholesterol levels. U.S.patent application Ser. Nos. and 10/090,038 and 11/136,794, disclose theuse of high doses of chromium complexes (providing between 1,000 and10,000 μg/day) and biotin for treating dyslipidemia, and increasingserum HDL levels.

Nicotinic acid and picolinic acid form coordination complexes withmonovalent, divalent and trivalent metal ions and facilitate theabsorption of these metals by transporting them across intestinal cellsand into the bloodstream.

Other compounds such as non-steroidal anti-inflammatory drugs (NSAIDs)such as aspirin and indomethachin have also been shown to facilitatechromium absorption. For Example, Davis et al. demonstrated that orallyadministered CrCl₃ is facilitated by the non-steroidal anti-inflammatorydrugs (NSAIDs) aspirin and indomethacin. Davis et al., 1995, J.Nutrition Res. 15:202-210 (1995); Kamath et al., 1997, J. Nutrition127:478-482. These drugs inhibit the enzyme cyclooxygenase whichconverts arachidonic acid to various prostaglandins, resulting ininhibition of intestinal mucus formation and lowering of intestinal pHwhich facilitates chromium absorption.

U.S. Pat. No. 4,315,927 teaches that when selected essential metals areadministered to mammals as exogenously synthesized coordinationcomplexes of picolinic acid, they are directly available for absorptionwithout competition from other metals. These complexes are safe,inexpensive, biocompatible and easy to produce.

SUMMARY

This application is based in part on the surprising discovery thatcertain chromium complexes, when provided in combination with starchand/or protein, provide an unexpected increase in amino acid absorption,protein synthesis, exercise tolerance, lean muscle mass, skeletal musclehypertrophy, muscle power, muscle endurance, muscle strength, FSR, anddecreasing delayed onset muscle soreness, muscle protein breakdown, andfat mass. In some aspects, the chromium complexes, when provided incombination with starch and/or protein can be used to treat and/orprevent muscle loss and/or sarcopenia.

Some embodiments provide a method for increasing muscle mass,comprising: administering an effective amount of a chromium complex anda starch in combination with an amount of a protein to a subject,wherein the subject's lean muscle mass is increased relative toproviding the amount of the protein alone.

Some embodiments provide a method for decreasing delayed onset musclesoreness, comprising: administering an effective amount of a chromiumcomplex and a starch in combination with an amount of a protein to asubject, wherein the subject's delayed onset muscle soreness isdecreased relative to providing the amount of the protein alone.

Some embodiments provide a method for increasing plasma levels ofessential amino acids, comprising: administering an effective amount ofa chromium complex and a starch in combination with an amount of aprotein to a subject, wherein the subject's plasma levels of essentialamino acids are increased relative to providing the amount of theprotein alone.

Some embodiments provide a method for increasing muscle uptake ofbranched chain amino acids, comprising: administering an effectiveamount of a chromium complex and a starch in combination with an amountof a protein to a subject, wherein the subject's muscle uptake ofbranched chain amino acids is increased relative to providing the amountof the protein alone.

Some embodiments provide a method of increasing a rate of musclehypertrophy comprising: administering an effective amount of a chromiumcomplex and a starch in combination with an amount of a protein to asubject temporally proximate to a resistance exercise, wherein thesubject's rate of muscle hypertrophy is increased relative to providingthe amount of the protein alone.

Some embodiments provide a method of increasing a fractional rate ofmuscle protein synthesis comprising: administering an effective amountof a chromium complex and a starch in combination with an amount of aprotein to a subject temporally proximate to a resistance exercise,wherein the subject's fractional rate of muscle protein synthesis isincreased relative to providing the amount of the protein alone.

Some embodiments provide a method of ameliorating muscle sorenesscomprising: identifying a subject suffering from muscle soreness; andadministering an effective amount of a chromium complex and a starch incombination with an amount of a protein to the subject, wherein thesubject's muscle soreness is decreased relative to providing the amountof the protein alone.

Some embodiments provide a method of increasing exercise staminacomprising: identifying a subject in need of increased exercise stamina;and administering an effective amount of a chromium complex and a starchin combination with an amount of a protein to a subject prior to anexercise, wherein the subject's exercise stamina is increased relativeto providing the amount of the protein alone.

Some embodiments further comprise administering a compound selected fromthe group consisting of caffeine, creatine, creatine hydrochloride,creatine monohydrate, taurine, guarana, vitamin C, vitamin B₁, vitaminB₂, vitamin B₃, vitamin B₅, vitamin B₆, vitamin B₇, vitamin B₉, andvitamin B₁₂, and combinations thereof.

In some embodiments, the protein is a whey protein. In some embodiments,the whey protein is hydrolyzed. In some embodiments, the protein sourceis branched chain amino acids. In some embodiments, the protein is avegetable protein. In some embodiments, the protein comprises at leastone essential amino acid. In some embodiments, the at least oneessential amino acid is leucine. In some embodiments, the starch isamylopectin.

In some embodiments, the chromium complex is selected from the groupconsisting of chromium picolinate, chromic tripicolinate, chromiumnicotinate, chromic polynicotinate, chromium chloride, chromiumhistidinate, chromium trihistidinate, and chromium yeasts, andcombinations thereof. In some embodiments, the chromium complex consistsessentially of chromium picolinate and chromium histidinate. In someembodiments, the chromium complex consists essentially of chromiumpicolinate. In some embodiments, the chromium complex consistsessentially of chromium histidinate. In some embodiments, the effectiveamount of the chromium and the starch is provided as a chromium-starchcomplex. In some embodiments, the amount of the protein is an amount ofthe protein consumed in a single day. In some embodiments, the amount ofthe protein is administered at least one hour after the effective amountof the chromium and the starch.

Some embodiments provide a nutritional supplement comprising: a firstamount of a chromium complex; and a second amount of amylopectin;wherein the first amount and the second amount are formulated as asingle dose and are effective to increase muscle mass in a subject.

In some embodiments, the chromium is present between about 0.001% (w/w)and about 3% (w/w). In some embodiments, the chromium is present betweenabout 0.005% (w/w) and about 2% (w/w). In some embodiments, the chromiumis present between about 0.01% (w/w) and about 1% (w/w). In someembodiments, the supplement is a solid. In some embodiments, the solidis a powder. In some embodiments, the supplement is a liquid. In someembodiments, the liquid is a concentrated formulation. In someembodiments, the supplement further comprises at least one of asweetener and a flavoring agent.

Some embodiments provide a method of making a composition comprisingchromium picolinate, chromium histidinate, at least one protein source,at least one starch, and at least one excipient, comprising: wet millingthe at least one protein source and the least one starch to form a firstmixture; spray drying the first mixture; and dry blending the firstmixture with chromium picolinate and chromium histidinate to form asecond mixture.

Some embodiments provide a method of stimulating muscle synthesis,comprising: identifying a person in need of increased muscle synthesis;and administering an effective amount of a chromium/amylopectin complexin combination with an amount of a protein, wherein thechromium/amylopectin complex causes increased muscle mass in a subjectcompared to a subject receiving a composition consisting essentially ofthe amount of the protein alone.

Some embodiments provide a method of treating muscle loss comprising:identifying a person in need of treatment for muscle loss; andadministering an effective amount of a chromium/amylopectin complex incombination with an amount of a protein, wherein thechromium/amylopectin complex causes increased muscle mass in a subjectcompared to a subject receiving a composition consisting essentially ofthe amount of the protein alone.

In some embodiments, the person is experiencing sarcopenia. In someembodiments, the administration of the chromium/amylopectin complexcauses increased muscle mass in a subject compared to a subjectreceiving the same diet without the chromium/amylopectin complex.

Some embodiments provide a method of increasing muscle power comprising:administering a composition having a chromium complex to provide a firstbioavailable amount of chromium to a subject and a starch source toprovide a second bioavailable amount of starch to the subject; andadministering an amount of a protein to the subject, wherein thesubject's muscle power is increased relative to administering acomposition consisting essentially of the amount of the protein alone.

Some embodiments provide a nutritional supplement comprising chromiumpicolinate, chromium histidinate, and amylopectin, wherein the chromiumand amylopectin are present in a weight ratio from at least about 1:1 toabout 1:2000. In some embodiments, the chromium is present between about100 mcg and about 2,000 mcg. In some embodiments, the chromium ispresent between about 500 mcg and about 1,500 mcg. In some embodiments,the chromium is present at about 1,000 mcg. In some embodiments, theamylopectin is present between about 100 mg and about 3,000 mg. In someembodiments, the amylopectin is present between about 1,000 mg and about2,500 mg. In some embodiments, the amylopectin is present between about1,500 mg and about 2,000 mg. In some embodiments, the amylopectin isderived from waxy maize.

Some embodiments provide a method for treating sarcopenia, comprising:administering an effective amount of a chromium complex and a starch incombination with an amount of a protein to a subject.

A method of treating muscle loss comprising: identifying a person inneed of treatment for muscle loss; and administering an effective amountof a chromium/amylopectin complex. In some embodiments, the person isexperiencing sarcopenia. In some embodiments, the person is elderly. Insome embodiments, the administration of the chromium/amylopectin complexcauses increased muscle mass in a subject compared to a subjectreceiving the same diet without the chromium/amylopectin complex.

Some embodiments provide a method for increasing muscle mass. Forexample, a method may include administering an effective amount of achromium complex to a subject in combination with a starch and aprotein. The subject's lean muscle mass may be increased relative toproviding the protein and starch alone. In another example, a method mayinclude administering an amount of chromium and starch to a subject. Thesubject may consume an amount of protein. The subject's lean muscle massmay be increased relative to consuming the amount of protein alone. Insome embodiments the muscle mass is increased by about 1 to 10%; 1.2 to9%; 1.4 to 8%; 1.6 to 7%; 1.8 to 6%; 2 to 5%; 3 to 4%; or any value inbetween. In some embodiments the muscle mass is increased by 1%, 2%, 3%,4%, 5%, 6%, 7%, 8%, 9%, 10%, or any value in between.

Some embodiments provide a method for decreasing delayed onset musclesoreness. For example, a method may include administering an effectiveamount of a chromium complex to a subject in combination with a proteinand a starch. The subject's delayed onset muscle soreness may bedecreased relative to providing protein and starch alone. In anotherexample, a method may include administering an amount of chromium andstarch to a subject. The subject may consume an amount of protein. Thesubject's onset muscle soreness may be decreased relative to consumingthe amount of protein alone. In some embodiments the delayed onsetmuscle soreness is decreased by about 10 to 100%; 15 to 95%; 20 to 90%;25 to 85%; 30 to 80%; 35 to 75%; 45 to 70%; or any value in between. Insome embodiments the delayed onset muscle soreness is decreased by 10%,20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any value in between.

Some embodiments provide a method for increasing plasma levels ofessential amino acids. For example, a method may include administeringan effective amount of a chromium complex to a subject in combinationwith a protein and a starch. The subject's plasma levels of essentialamino acids may be increased relative to providing protein and starchalone. In another example, a method may include administering an amountof chromium and starch to a subject. The subject may consume an amountof protein. The subject's plasma levels of essential amino acids may beincreased relative to consuming the amount of protein alone. In someembodiments the plasma levels of essential amino acids is increased byabout 5 to 100%; 10 to 90%; 15 to 80%; 20 to 70%; 25 to 60%; 30 to 50%;35 to 40%; or any value in between. In some embodiments the plasmalevels of essential amino acids is increased by 5%, 10%, 15%, 20%, 30%,40%, 50%, 60%, 70%, 80%, 90%, or any value in between. In someembodiments, the essential amino acids are selected from phenylalanine,valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine,and histidine. In some embodiments, the essential amino acids areleucine and/or isoleucine.

Some embodiments provide a method for increasing muscle uptake ofbranched chain amino acids. For example, a method may includeadministering an effective amount of a chromium complex in combinationwith a protein and a starch to a subject. The subject's muscle uptake ofbranched chain amino acids may be increased relative to providingprotein and starch alone. In another example, a method may includeadministering an amount of chromium and starch to a subject. The subjectmay consume an amount of protein. The subject's uptake of branched chainamino acids may be increased relative to consuming the amount of proteinalone. In some embodiments the muscle uptake of branched chain aminoacids is increased by about 5 to 100%; 10 to 90%; 15 to 80%; 20 to 70%;25 to 60%; 30 to 50%; 35 to 40%; or any value in between. In someembodiments the muscle uptake of branched chain amino acids is increasedby 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or any value inbetween. In some embodiments, the branched chain amino acids areselected from valine, threonine, leucine, and isoleucine. In someembodiments, the branched chain amino acids amino acids are leucineand/or isoleucine.

Some embodiments provide a method of increasing rate of musclehypertrophy. For example, a method may include administering aneffective amount of a chromium complex in combination with a protein anda starch to a subject. The administration may be temporally proximate toresistance exercise. The subject's rate of muscle hypertrophy may beincreased relative to providing protein and starch alone. In anotherexample, a method may include administering an amount of chromium andstarch to a subject. The subject may consume an amount of protein. Thesubject's rate of muscle hypertrophy may be increased relative toconsuming the amount of protein alone. In some embodiments the rate ofmuscle hypertrophy is increased by about 1 to 10%; 1.2 to 9%; 1.4 to 8%;1.6 to 7%; 1.8 to 6%; 2 to 5%; 3 to 4%; or any value in between. In someembodiments the rate of muscle hypertrophy is increased by 1%, 2%, 3%,4%, 5%, 6%, 7%, 8%, 9%, 10%, or any value in between.

Some embodiments provide a method of increasing the fractional rate ofmuscle protein synthesis. For example, a method may includeadministering an effective amount of a chromium complex in combinationwith a protein and a starch to a subject. The administration may betemporally proximate to resistance exercise. The subject's fractionalrate of muscle protein synthesis may be increased relative to providingprotein and starch alone. In another example, a method may includeadministering an amount of chromium and starch to a subject. The subjectmay consume an amount of protein. The consumption of protein may betemporally proximate to resistance exercise. The subject's rate ofmuscle protein synthesis may be increased relative to consuming theamount of protein alone. In some embodiments the fractional rate ofmuscle protein synthesis is increased by about 1 to 10%; 1.2 to 9%; 1.4to 8%; 1.6 to 7%; 1.8 to 6%; 2 to 5%; 3 to 4%; or any value in between.In some embodiments the fractional rate of muscle protein synthesis isincreased by 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or any value inbetween.

Some embodiments provide a method of ameliorating muscle soreness. Forexample, a method may include identifying a subject suffering frommuscle soreness and administering an effective amount of a chromiumcomplex in combination with a protein and a starch to the subject. Thesubject's muscle soreness may be decreased relative to providing proteinand starch alone. In another example, a method may include administeringan amount of chromium and starch to a subject. The subject may consumean amount of protein. The subject's muscle soreness may be decreased inless time relative to consuming the amount of protein alone. In someembodiments the muscle soreness is ameliorated by about 10 to 100%; 15to 95%; 20 to 90%; 25 to 85%; 30 to 80%; 35 to 75%; 45 to 70%; or anyvalue in between. In some embodiments the muscle soreness is amelioratedby 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any value inbetween.

Some embodiments provide a method of increasing exercise stamina. Forexample, a method may include identifying a subject in need of increasedexercise stamina and administering an effective amount of a chromiumcomplex in combination with a protein and a starch to the subject. Theadministration may be prior to beginning exercise. The subject'sexercise stamina may be increased relative to providing protein andstarch alone. In another example, a method may include administering anamount of chromium and starch to a subject. The subject may consume anamount of protein. The subject's stamina may be increased relative toconsuming the amount of protein alone. In some embodiments the exercisestamina is increased by about 1 to 20%; 2 to 18%; 3 to 17%; 4 to 16%; 5to 15%; 6 to 14%; 7 to 12%; or any value in between. In some embodimentsthe exercise stamina is increased by 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%,10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, or any value inbetween.

Some embodiments provide a method of treating or preventing muscle loss.For example, a method may include identifying a subject in the need of atreatment to prevent muscle loss. Such a subject may have sarcopenia.The method may include administering an effective amount of a chromiumcomplex in combination with a starch to the subject. The subject'smuscle loss may be stopped and/or reversed. In another example, a methodmay include administering an amount of chromium and starch to a subject.The subject may consume an amount of protein. The subject's muscle lossmay be stopped and/or reversed. In some embodiments the muscle loss isreduced by about 10 to 100%; 15 to 95%; 20 to 90%; 25 to 85%; 30 to 80%;35 to 75%; 45 to 70%; or any value in between. In some embodiments themuscle loss is reduced by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%,100%, or any value in between.

Some embodiments provide a method of increasing FSR. For example, themethod may include administering an effective amount of a chromiumcomplex in combination with a protein and a starch to a subject, whichincreases FSR relative to an equivalent dose of protein and starchalone. In some embodiments, the method may include administering aneffective amount of a chromium complex in combination with a protein anda starch to a subject, which provides an equivalent FSR relative to ahigher dose of protein and starch alone. In some embodiments, the doseof protein and starch alone is 1.3-fold, 1.5-fold, 1.8-fold, 2-fold,2.3-fold, 2.5-fold, 2.8-fold, 3-fold, 3.3-fold, 3.5-fold, 3.8-fold,4-fold, 4.3-fold, 4.5-fold, 4.8-fold, or 5-fold higher, or any value inbetween.

Some embodiments further comprise administering a compound selected fromcaffeine, creatine, creatine hydrochloride, creatine monohydrate,taurine, guarana, vitamin C, vitamin B1, vitamin B2, vitamin B3, vitaminB5, vitamin B6, vitamin B7, vitamin B9, and vitamin B12, or anycombination of the foregoing.

In some embodiments, the protein is whey protein. In some embodiments,the whey protein is hydrolyzed. In some embodiments, the starch isamylopectin.

In some embodiments, the chromium complex is selected from chromiumpicolinate, chromic tripicolinate, chromium nicotinate, chromicpolynicotinate, chromium chloride, chromium histidinate, chromiumtrihistidinate, and chromium yeasts, or any combination of theforegoing. In some embodiments, the chromium complex is selected fromchromium picolinate, chromic tripicolinate, chromium histidinate,chromium trihistidinate and a combination of any of the foregoing.

In some embodiments, the chromium complex consists essentially ofchromium picolinate and chromium histidinate. In some embodiments, thechromium complex consists essentially of chromium picolinate. In someembodiments, the chromium complex consists essentially of chromiumhistidinate.

Some embodiments provide a nutritional supplement. The supplement mayinclude a first amount of a Chromium/Amylopectin Complex. The supplementmay also include a second amount of protein. The first amount of theChromium/Amylopectin Complex may be provided in an amount that causes anincrease in muscle mass in a subject to a greater extent than providinga composition consisting essentially of the second amount of protein.

In some embodiments, the chromium is present between about 0.001% (w/w)to about 3% (w/w). In some embodiments, the chromium is present betweenabout 0.005% (w/w) to about 2% (w/w). In some embodiments, thesupplement is a solid. In some embodiments, the solid is a powder. Insome embodiments, the supplement is a liquid. In some embodiments, theliquid is a concentrated formulation. In some embodiments, thesupplement further comprises at least one of a sweetener and a flavoringagent.

Some embodiments provide a method of making a composition comprisingchromium picolinate, chromium histidinate, at least one protein source,at least one starch, and at least one excipient. The method may includewet milling the at least one protein source and the least one starch toform a first mixture, spray drying the first mixture, and dry blendingthe first mixtures with chromium picolinate and chromium histidinate toform a second mixture.

Some embodiments provide a method of stimulating muscle synthesiscomprising identifying a person in need of increased muscle synthesis.For example, a method may include administering an effective amount of aChromium/Amylopectin Complex in combination with an amount of protein.The Chromium/Amylopectin Complex may cause an increase in muscle mass ina subject compared to a subject receiving a composition consistingessentially of the amount of protein and amylopectin alone.

Some embodiments provide a nutritional supplement comprising chromiumpicolinate, chromium histidinate, and amylopectin, wherein the chromiumand amylopectin are present in a ratio from at least about 1:1 to about1:2000, or any ratio in between. Some embodiments provide a nutritionalsupplement comprising chromium picolinate, chromium histidinate, andamylopectin, wherein the chromium and amylopectin are present in a ratioof 1:1, 1:5, 1:10, 1:20, 1:50, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600,1:700, 1:800, 1:900, 1:1000, 1:1200, 1;1400, 1:1600, 1:1800, 1:2000, orany ratio in between. In some embodiments, the chromium and amylopectinare present in a ratio of about 1:1 to about 1:2000, about 1:10 to about1:1800, about 1:20 to about 1:1600, about 1:40 to about 1:1400, about1:60 to about 1:1200, about 1:80 to about 1:1000, about 1:100 to about1:800, about 1:150 to about 1:600, about 1:200 to about 1:400, or anyratio in between.

In some embodiments, the total chromium present in the composition isbetween about 10 mcg to about 2,000 mcg. In some embodiments, the totalchromium present in the composition is between about 10 to about 2,000mcg, about 50 to about 1,800 mcg, about 100 to about 1,600 mcg, about200 to about 1,400 mcg, about 300 to about 1,200 mcg, about 400 to about1000 mcg, about 500 to about 800 mcg, or any amount in between.

In some embodiments, the amylopectin is present between about 100 mg toabout 3,000 mg, or any amount in between. In some embodiments, theamylopectin is present between about 1,000 mg to about 2,500 mg, or anyamount in between. In some embodiments, the amylopectin is presentbetween about 1,500 mg to about 2,000 mg, or any amount in between. Insome embodiments, the amylopectin is derived from waxy maize.

In some embodiments, the chromium is selected from chromium picolinate,chromic tripicolinate, chromium nicotinate, chromic polynicotinate,chromium chloride, chromium histidinate, chromium trihistidinate, andchromium yeasts, or any combination of the foregoing. In someembodiments, the chromium consists essentially of chromium picolinateand chromium histidinate. In some embodiments, the chromium consistsessentially of chromium picolinate. In some embodiments, the chromiumconsists essentially of chromium histidinate.

In some embodiments, the composition comprises about 500 mcg chromiumfrom chromium histidinate, about 500 mcg of chromium from chromiumpicolinate, and about 2,000 mg amylopectin. In some embodiments, thecomposition further comprises about 5 to about 20 grams of an amino acidsource. In some embodiments, the amino acid source is whey protein. Insome embodiments, the composition is formulated for combining with aprotein shake or workout recovery beverage.

In some embodiments, the nutritional supplement further comprises acompound selected from caffeine, creatine, creatine hydrochloride,creatine monohydrate, taurine, guarana, vitamin C, vitamin B1, vitaminB2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, andvitamin B12, or any combination of the foregoing. Any of the features ofan embodiment is applicable to all other embodiments identified herein.Moreover, any of the features of an embodiment is independentlycombinable, partly or wholly with other embodiments described herein inany way, e.g., one, two, or three or more embodiments may be combinablein whole or in part. Further, any of the features of an embodiment maybe made optional to other embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 and FIG. 2 illustrate changes in mean±SD plasma essential aminoacids (EAAs). Although within-trial increases were statisticallysignificant for both Trial A and Trial B at various time points (i.e.270 min, 300 min), no overall or between-group (pairwise) differenceswere noted.

FIG. 3 , FIG. 4 , and FIG. 5 illustrate changes in mean±SD plasmainsulin. Two-way ANOVA revealed a trend (P=0.09) for a differencebetween trials. Within-trial increases were statistically significantfor only Trial A at all time points after 240 min (i.e. 270 min, 300min, 330 min, 360 min, 390 min, and 480 min).

FIGS. 6, 6A, and 6B illustrate changes in mean±SD plasma glucose. Whilethe two-way ANOVA was not significant (P=0.22) for a difference betweentrials, within-trial increases were statistically significant for onlyTrial A at all time points after 300 min (i.e. 330 min, 360 min, 390min, and 480 min).

FIG. 7 illustrates peak increases in mean±SD plasma leucine occurred 30minutes after the oral ingestion of whey protein+CrPic/CrHis+amylopectin(WCAP), (i.e. at 270 min) and were significantly different from baseline(P<0.001). However, no overall interaction was noted (P=0.22), andpair-wise differences were not statistically significant between trialsat any time point.

FIG. 8 illustrates peak increases in mean±SD plasma isoleucine occurred30 minutes after the oral ingestion of WCAP, (i.e. at 270 min) and weresignificantly different from baseline (P<0.001). However, no overallinteraction was noted (P=0.24), and pair-wise differences were notstatistically significant between trials at any time point.

FIG. 9 illustrates peak increases in mean±SD plasma valine occurred 30minutes after the oral ingestion of WCAP, (i.e. at 270 min) and weresignificantly different from baseline (P<0.02). However, no overallinteraction was noted (P=0.66), and pair-wise differences were notstatistically significant between trials at any time point.

FIG. 10 illustrates peak increases in mean±SD plasma methionine occurred30 minutes after the oral ingestion of WCAP, (i.e. at 270 min) and weresignificantly different from baseline (P<0.006). However, no overallinteraction was noted (P=0.81), and pair-wise differences were notstatistically significant between trials at any time point.

FIG. 11 illustrates peak increases in mean±SD plasma histidine occurred30 minutes after the oral ingestion of WCAP, (i.e. at 270 min) andtended to be significantly different from baseline in Trial A only(P=0.06). However, no overall interaction was noted (P=0.58), andpair-wise differences were not statistically significant between trialsat any time point.

FIG. 12 illustrates peak increases in mean±SD plasma phenylalanineoccurred 30 minutes after the oral ingestion of WCAP, (i.e. at 270 min)and were significantly different from baseline (P<0.001). Values at 240min and 300 min were also significantly greater in both Trials (comparedto their respective baseline). However, no overall interaction was noted(P=0.28), and pair-wise differences were not statistically significantbetween trials at any time point.

FIG. 13 illustrates peak increases in mean±SD plasma threonine occurred30 minutes after the oral ingestion of WCAP, (i.e. at 270 min) and weresignificantly different from baseline (P<0.01) during Trial A only.However, no overall interaction was noted (P=0.62), and pair-wisedifferences were not statistically significant between trials at anytime point.

FIG. 14 illustrates peak increases in mean±SD plasma lysine occurred 30minutes after the oral ingestion of WCAP, (i.e. at 270 min) and weresignificantly different from baseline (P<0.006). However, no overallinteraction was noted (P=0.43), and pair-wise differences were notstatistically significant between trials at any time point.

FIG. 15 illustrates peak increases in mean±SD plasma tryptophan occurred30 minutes after the oral ingestion of WCAP, (i.e. at 270 min) and weresignificantly different from baseline (P<0.03). However, no overallinteraction was noted (P=0.80), and pair-wise differences were notstatistically significant between trials at any time point.

FIG. 16 illustrates mean±SD changes in muscle fractional proteinsynthesis rate (FSR) using plasma precursor enrichment. Three-way ANOVA(Trial×Gender×Time) was not significant, P=0.59. Two-way ANOVA was notsignificant (P=0.36); however, one-way ANOVA revealed a statisticallysignificant (within-trial) increase during the Active trial only(P=0.001).

The results indicate that the Active trial yielded a more robustresponse 32%) in FSR versus the Control trial (21%; P=0.001).Specifically, in the Active trial, pre-treatment FSRpl was 0.0507±0.01%and post-treatment FSRpl was 0.0745±0.016%. In the Control trial,pre-treatment FSRic was 0.0532±0.023% while post-treatment FSRic was0.0647±0.013%. The significant response of the Active trial was achievedin light of similar leucine and essential amino acid concentrationsresultant from each treatment. A potential explanation for improvedresponse of the Active trial may lie in its insulinogenic properties.Peak insulin response of the Active trial trended towards significance(p=0.09).

FIG. 17 illustrates mean±SD changes in FSR using intracellular precursorenrichment. Three-way ANOVA (Trial×Gender×Time) was not significant,P=0.37. Two-way ANOVA was not significant (P=0.30); however, one-wayANOVA revealed a statistically significant (within-trial) increaseduring the Active trial only (P=0.001).

FIG. 18 illustrates that increasing doses of protein alone increased FSRup to a ceiling at 2.33 grams protein/kg. Administration of WCAPprovided an unexpectedly significant increase in FSR even at proteinlevels over the maximum FSR achieved with protein alone, i.e., WCAPincreases the protein ceiling relative to whey protein alone. The FSR oflower doses of WCAP also unexpectedly provided enhanced proteinsynthesis that were equivalent to FSR levels achieved with substantiallyhigher doses of protein alone.

FIG. 19 illustrates that WCAP increases the maximum FSR levels comparedto an equivalent dose of protein alone (vertical arrow). FIG. 19 alsoillustrates that low doses of WCAP provide equivalent FSR levels to muchhigher doses of protein alone (horizontal arrow).

DETAILED DESCRIPTION

Definitions

The terminology used in the description presented herein is not intendedto be interpreted in any limited or restrictive manner, simply becauseit is being utilized in conjunction with a detailed description ofcertain specific embodiments described herein. Furthermore, embodimentsdescribed herein can include several novel features, no single one ofwhich is solely responsible for its desirable attributes or which isessential to practicing the invention herein described.

Embodiments relate to the use of compositions comprising, consistingessentially of, or consisting of chromium and at least one starch. Thechromium may be provided as chromium and histidine, a chromiumhistidinate complex, chromium trihistidinate, a chromium polyhistidinate complex, or combinations thereof, including pharmaceuticallyacceptable salts, hydrates, solvates, or mixtures thereof in combinationwith a second slow-acting chromium complex for the treatment orprevention of cardiometabolic syndrome and related conditions, diseases,and disorders.

The term “treating” or “treatment” as used herein is a broad term, andis to be given its ordinary and customary meaning to a person ofordinary skill in the art (and is not to be limited to a special orcustomized meaning), and does not necessarily mean total cure. Anyalleviation of any undesired signs or symptoms of the disease to anyextent or the slowing down of the progress, or even prevention of thedisease or condition can be considered treatment. As used herein, theterm “providing” (a substance) as used herein is a broad term, and is tobe given its ordinary and customary meaning to a person of ordinaryskill in the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to supplying, making available,or administering the substance. As used herein, the term “temporallyproximate” (to an event) refers to a time about two hours before, to twohours after, the event, including during the event. As used herein, theterm “resistance exercise” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to any exercise that causes themuscles to contract against an external resistance, for example aweighted bar, or against body weight. As used herein, the term “subject”as used herein is a broad term, and is to be given its ordinary andcustomary meaning to a person of ordinary skill in the art (and is notto be limited to a special or customized meaning), and refers withoutlimitation to animals, preferably mammals, and most preferably humans.The term “subject” may be used interchangeably with “patient” and with“person.”

The compositions described herein can contain one or more chiral centersand/or double bonds and, therefore, exist as stereoisomers, such asdouble-bond isomers (i.e., geometric isomers), enantiomers, ordiastereomers. The chemical structures depicted herein, and thereforethe compositions of the embodiments, encompass all of the correspondingcompounds' or compositions' enantiomers and stereoisomers, that is, boththe stereomerically pure form (e.g., geometrically pure,enantiomerically pure, or diastereomerically pure) and enantiomeric andstereoisomeric mixtures.

As used herein, a composition that “substantially” comprises a compoundmeans that the composition contains more than about 80% by weight, morepreferably more than about 90% by weight, even more preferably more thanabout 95% by weight, and most preferably more than about 97% by weightof the compound. As used herein, a composition that “substantially”comprises a chromium complex refers to a composition that contains morethan or equal to 7.0% of trivalent or dietary chromium. Preferably, acertificate of analysis for the compositions indicate that thecompositions are negative for microbial growth, yeast and mold should bepresent in less than 300 cells/g and the toxic metals should be lessthan 1 ppm.

In some embodiments, the compositions are in the form ofpharmaceutically effective salts. The phrase “pharmaceuticallyacceptable salt(s),” as used herein includes, but is not limited to,salts of acidic or basic groups that may be present in the compositions.Compounds that are basic in nature are capable of forming a wide varietyof salts with various inorganic and organic acids. The acids that may beused to prepare pharmaceutically acceptable acid addition salts of suchbasic compounds are those that form non-toxic acid addition salts, i.e.,salts containing pharmacologically acceptable anions, including but notlimited to sulfuric, citric, maleic, acetic, oxalic, hydrochloride,hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acidphosphate, isonicotinate, acetate, lactate, salicylate, citrate, acidcitrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate,succinate, maleate, gentisinate, fumarate, gluconate, glucaronate,saccharate, formate, benzoate, glutamate, methanesulfonate,ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e.,1,1′-methylene-bis-(2-hydroxy-3-naphthoate)) salts. Compounds present inthe compositions that include an amino moiety also can formpharmaceutically acceptable salts with various amino acids, in additionto the acids mentioned above. Compounds present in the compositions thatare acidic in nature are capable of forming base salts with variouspharmacologically acceptable cations. Non limiting examples of suchsalts include alkali metal or alkaline earth metal salts and,particularly, calcium, magnesium, sodium lithium, zinc, potassium,silicon, phosphorus and iron salts.

As used herein, the term “hydrate” means a compound or a salt thereof,that further includes a stoichiometric or non-stoichiometric amount ofwater bound by non-covalent intermolecular forces. The term hydrateincludes solvates, which are stoichiometric or non-stoichiometricamounts of a solvent bound by non-covalent intermolecular forces.Preferred solvents are volatile, non-toxic, and/or acceptable foradministration to humans in trace amounts.

The amount of a compound of the embodiments that will be effective inthe treatment of a particular disorder or condition will depend on thenature of the disorder or condition, and can be determined by standardclinical techniques. In addition, in vitro or in vivo assays mayoptionally be employed to help identify optimal dosage ranges. Theprecise dose to be employed in the compositions will also depend on theroute of administration, and the seriousness of the disease or disorder,and should be decided according to the judgment of the practitioner andeach circumstances. However, suitable dosage ranges for oraladministration are generally about 0.001 milligram to 5000 milligrams ofa total chromium complex per kilogram body weight. In preferredembodiments, the oral dose is 0.01 milligram total chromium complex to1000 milligrams per kilogram body weight, more preferably 0.1 milligramto 100 milligrams per kilogram body weight, more preferably 0.5milligram to 25 milligrams per kilogram body weight, and yet morepreferably 1 milligram to 10 milligrams per kilogram body weight. Thedosage amounts described herein refer to total amounts administered;that is, if more than one chromium complex or more than one compositionis administered, the preferred dosages correspond to the total amount ofthe compositions administered. Oral compositions preferably contain 10%to 95% active ingredient.

The compositions can preferably be formulated with other activeingredients as a slow-acting agent or long acting agent in addition todrugs or alone before meals and/or after meals. Effective doses may beextrapolated from dose-response curves derived from in vitro or animalmodel test systems. Such animal models and systems are well known in theart.

In accordance with the methods, the amount of chromium provided by thecompositions that comprise at least 50 μg per dose, for example at least60 μg, at least 70 μg, at least 80 μg, at least 90 μg, at least 100 μg,at least 125 μg, at least 150 μg, at least 200 μg, at least 250 μg, atleast 300 μg, at least 350 μg, at least 400 μg, at least 450 μg, atleast 500 μg, at least 550 μg, at least 600 μg, at least 650 μg, atleast 700 μg, at least 750 μg, at least 800 μg, at least 850 μg, atleast 900 μg, at least 950 μg, at least 1,000 μg, at least 1500 μg, atleast 2,000 μg, at least 2500 μg, at least 3000 μg, at least 3500 μg, atleast 4000 μg, at least 4500 μg or at least 5000 μg chromium per dose.In some aspects, the amount of chromium may be formulated to provide acertain amount of bioavailable chromium. For example, the compositionsmay provide at least 1-2,000 μg of bioavailable chromium per day.

In some aspects, chromium is provided in the form of a fast-actingchromium complex and a slow-acting chromium complex. The fast-actingcomplex may be absorbed more quickly than the slow-acting chromiumcomplex. For example, in some embodiments, a lipophilic chromium complexor slow-acting chromium complex can be chromium picolinate or chromiumtripicolinate, and the hydrophilic chromium complex or fast-actingchromium complex can be any one of chromium acetate, chromium chloride,chromium histidinate, and chromium nicotinate, or any combinationthereof. In some embodiments, the hydrophilic chromium complex orfast-acting chromium complex is chromium histidinate. In someembodiments, a slow-acting or lipophilic chromium complex is chromiumpicolinate. The fast-acting and the slow-acting chromium complexes canbe provided to a subject such that the ratio of chromium in the form ofa “fast-acting” chromium complex to the chromium in the form of a“slow-acting” chromium complex is anywhere from 10:1 to 1:10, e.g., 9:1,8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7,1;8, 1:9, 1:10, or any fraction in between. In some embodiments, theratio of chromium provided in the form of a fast-acting chromium complexto the slow-acting chromium complex is 1:1.

By way of example, the level of chromium used for supplementation inorder to inhibit the onset of insulin resistance is at least about 50μg/day. Chromium picolinate and chromium chloride have been administeredto rats at levels several thousand times the upper limit of theestimated safe and adequate daily dietary intake (ESADDI) for chromiumfor humans (based on body weight) without toxic effects. R. Anderson etal., Lack of Toxicity of Chromium Chloride and Picolinate, 16 J. Am.Coll. Nutr. 273-279 (1997). While the level of chromium, in the form offast-acting and slow-acting chromium complexes, used for supplementationmay be within several thousand times the upper limit of the ESADDI,preferably, the total amount of chromium provided by the fast-acting andslow-acting complexes is between about 50 and 2,000 μg/day. Morepreferably, the amount of total chromium provided by the fast-acting andslow-acting complexes is between about 100 and 2,000 μg/day. Mostpreferably, the amount of total chromium is between about 400 and 1,000μg/day. In a particularly preferred embodiment, the amount of totalchromium is between about 600 and 1,000 μg/day. These doses are based ona 70 kg adult human, and that the dose can be applied on a per-kilogrambasis to humans or animals of different weights.

Advantageously, an individual is administered a pharmaceuticallyeffective dose of a hydrophilic chromium complex such as chromiumhistidinate in combination with at least one other lipophilic chromiumcomplex, such as chromium picolinate. In some embodiments, a compositionthe fast-acting and a slow-acting chromium complexes are administeredsubstantially simultaneously. In an alternative embodiment, thefast-acting, hydrophilic and slow-acting, lipophilic chromium complexesare provided to the subject sequentially in either order. Ifadministered separately, the fast-acting and slow-acting chromiumcomplex should be given in a temporally proximate manner, e.g., within atwenty-four hour period. More particularly, a fast-acting and aslow-acting chromium complex can be given within one hour of each other.One of skill in the art will appreciate that other components may beadded separately or incorporated into a single formulation to enhancethe effects of chromium.

In some embodiments, the compositions can be provided prior to orconcomitantly with an insulin resistance-inducing food. Insulinresistance-inducing foods generally have high glycemic indexes, e.g.,over 50. In other embodiments, the compositions are provided after theinsulin resistance inducing food. In embodiments wherein thecompositions and the insulin resistance-inducing foods are not providedconcomitantly, the composition and the food are preferably provided in atemporally proximate manner, e.g., within twenty four hours, and morepreferably within one hour.

In some embodiments, the compositions can be provided prior to orconcomitantly with a high-protein meal or protein supplement. In someembodiments, the compositions can be provided once daily, up to sixtimes daily. In some embodiments, the compositions can be provided priorto or concomitantly with each meal during the day. In some embodiments,the compositions can be provided prior to or concomitantly with eachsnack during the day. In some embodiments, the compositions can beprovided prior to or concomitantly with each meal and each snack duringthe day.

In some embodiments, the compositions can be provided prior to orconcomitantly to aerobic training. In some embodiments, the compositionscan be provided prior to or concomitantly to anaerobic training. In someembodiments, the compositions can be provided concomitantly with otherexercise supplements, including, but not limited to caffeine, creatine,creatine hydrochloride, creatine monohydrate, taurine, guarana, vitaminC, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₅, vitamin B₆, vitaminB₇, vitamin B₉, and vitamin B₁₂, or any combination of the foregoing.

In some embodiments, uncomplexed chelating agents are advantageouslyincluded in the compositions to facilitate absorption of other ingestedchromium as well as other metals including, but not limited to, copper,iron, magnesium, manganese, and zinc. Suitable chelating agents includehistidine, any essential amino D or L amino acids, tri amino acidformulae including but not limited to, triphenylalanine, trihistidine,triarginine, picolinic acid, nicotinic acid, or both picolinic acid andnicotinic acid. Thus, the compositions of the embodiments are readilyabsorbable forms of chromium complex which also facilitate absorption ofother essential metals in the human diet. In some embodiments, certainchelating agents may be added to facilitate absorption of the chromiumcomplex, or combination of chromium complexes in the compositions.Chelating agents such as histidine, picolinic acid and nicotinic acidare available from many commercial sources, including Sigma-Aldrich (St.Louis, MO) (picolinic acid; catalog No. P5503; nicotinic acid; catalogNo. PN4126). Preferably, the ratio of either the fast-acting, orslow-acting, or the combination of the fast-acting and slow-actingchromium complex to the chelating agent from about 10:1 to about 1:10(w/w), more preferably from about 5:1 to about 1:5 (w/w). Alternatively,the molar ratio of chromium complex to the uncomplexed chelating agentis preferably 1:1, and may be from about 5:1 to about 1:10. Thechelating agents with D or L amino acid and or with tri or mono and diforms of chromium complex with tri amino acid or one or more amino acidsbut not limited to chromium triphenylanine, chromium trihistidine,chromium polyphenylanine, chromium poly hisitidine, chromiumpolynicotinate, chromium diphenylananine, chromium dipicolinic acid,chromium dihisitidine etc. More than one chelating agent, e.g., bothnicotinic and picolinic acid can be included in the compositions, oradministered to subject in the methods described herein.

Certain embodiments also include an amino acid source. Exemplary aminoacid sources include, but are not limited to whey protein, caseinprotein, egg protein, pea protein, rice protein, soy protein, beefprotein, hemp protein, vegetable protein and combinations of any of theforegoing. The amino acid source may optionally by hydrolyzed. Theprotein source is optionally an isolate of one or more of the proteinsources described above. The source of protein may be administered atthe same time as the chromium and/or starch or at a different time. Therelative amounts of amino acids to starch to chromium may vary. In someembodiments, the amino acid source comprises about 1 gram of protein toabout 30 grams of protein, or any value in between. In some embodiments,the amino acid source comprises about 1 to about 30 grams, about 2 toabout 25 grams, about 3 to about 20 grams, about 4 to about 15 grams,about 5 to about 10 grams of protein, or any amount in between.

Certain embodiments also include one or more starches or saccharides.Exemplary saccharides include, but are not limited to glucose, sucrose,fructose, maltose, maltodextrin, dextrin, amylose, pectin, andamylopectin. The compositions may include at least 1,000 mg per day, forexample at least 50 mg, at least 70 mg, at least 80 mg, at least 90 mg,at least 100 mg, at least 125 mg, at least 150 mg, at least 200 mg, atleast 250 mg, at least 300 mg, at least 350 mg, at least 400 mg, atleast 450 mg, at least 500 mg, at least 550 mg, at least 600 mg, atleast 650 mg, at least 700 mg, at least 750 mg, at least 800 mg, atleast 850 mg, at least 900 mg, at least 950 mg, at least 1,000 mg, atleast 1500 mg, at least 2,000 mg, at least 2500 mg, at least 3000 mg, atleast 3500 mg, at least 4000 mg, at least 4500 mg or at least 5000 mg ofamylopectin per dose. In some aspects, the amount of amylopectin may beformulated to provide a certain amount of bioavailable amylopectin. Forexample, the compositions may provide at least 1-5,000 mg ofbioavailable amylopectin per day. The chromium and the amylopectin canbe provided to a subject such that the ratio of chromium to theamylopectin is anywhere from 1:2,000 or any fraction in between.

In general, the compositions may be formulated such that the starch andthe chromium are delivered at the same time or at substantially the sametime. In some aspects, the starch and chromium may form achromium-starch complex. That is to say, one or more starches andchromium ions may be associated with each other and administered in sucha manner. For example, the composition may include one or morechromium/amylopectin complexes and/or conformations.

The compositions comprising, for example, chromium and amylopectin maybe dosed a plurality of times per day. For example, the composition maybe administered once per day or twice per day or three times per day orfour times per day or five times per day or six times per day. Thecomposition may be administered before or after a meal or a set timeinterval before or after a meal. The composition may be administeredimmediately before or after immediately exercise. The composition mayalso be administered at a set time interval before or after exercise.

The administration of the compositions can be by any of the methods ofadministration described below or by delivery methods known by one ofskill in the art. The compositions may be administered orally, throughparenteral nutrition, e.g., feeding tube or intravenously, and throughother known means. Chromium histidinate in combination with otherchromium complexes or essential nutrients but not limited to fattyacids, carbohydrates, minerals and vitamins etc. is a particularlypreferred source fast-acting chromium complex due to its high level ofbioavailability, but other fast-acting, hydrophilic chromium complex canalso be used.

Some embodiments provide at least 50 mcg bioavailable chromium. Someembodiments provide at least 100 mcg bioavailable chromium. Someembodiments provide at least 150 mcg bioavailable chromium. Someembodiments provide at least 250 mcg bioavailable chromium. Someembodiments provide at least 50 mcg bioavailable chromium in about 30minutes. Some embodiments provide at least 100 mcg bioavailable chromiumin about 1 hour. Some embodiments provide at least 200 mcg bioavailablechromium in about 2 hours. Some embodiments provide at least 200 mcgbioavailable chromium in about 4 hours.

Some embodiments provide at least 500 mcg bioavailable chromium. Someembodiments provide at least 750 mcg bioavailable chromium. Someembodiments provide at least 1,000 mcg bioavailable chromium. Someembodiments provide at least 1,250 mcg bioavailable chromium. Someembodiments provide at least 500 mcg bioavailable chromium in about 30minutes. Some embodiments provide at least 750 mcg bioavailable chromiumin about 1 hour. Some embodiments provide at least 1,000 mcgbioavailable chromium in about 2 hours. Some embodiments provide atleast 1,000 mcg bioavailable chromium in about 4 hours.

Some embodiments provide an increased amount of bioavailable starchrelative to starch alone. Some embodiments provide an increased amountof bioavailable protein relative to protein alone. Some embodimentsprovide an increased amount of bioavailable protein and starch relativeto protein and starch alone. In some embodiments, the bioavailability isincreased by at least about 10%, at least about 20%, at least about 30%,at least about 40%, at least about 50%, at least about 60%, at leastabout 70%, at least about 80%, at least about 90%, at least about 95%,or at least about 99%.

For oral administration, the compositions can be provided as a tablet,aqueous or oil suspension, dispersible powder or granule, emulsion, hardor soft capsule, syrup, elixir, or beverage. Compositions intended fororal use can be prepared according to any method known in the art forthe manufacture of pharmaceutically acceptable compositions and suchcompositions may contain one or more of the following agents:sweeteners, flavoring agents, coloring agents and preservatives. Thesweetening and flavoring agents will increase the palatability of thepreparation. Tablets containing chromium complexes in admixture withnon-toxic pharmaceutically acceptable excipients suitable for tabletmanufacture are acceptable. Pharmaceutically acceptable vehicles such asexcipients are compatible with the other ingredients of the formulation(as well as non-injurious to the patient). Such excipients include inertdiluents such as calcium carbonate, sodium carbonate, lactose, calciumphosphate or sodium phosphate; granulating and disintegrating agents,such as corn starch or alginic acid; binding agents such as starch,gelatin or acacia; and lubricating agents such as magnesium stearate,stearic acid or talc. Tablets can be uncoated or can be coated by knowntechniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a sustained action over alonger period of time. For example, a time delay material such asglyceryl monostearate or glyceryl distearate alone or with a wax can beemployed.

Formulations for oral use can also be presented as hard gelatin capsuleswherein the active ingredient is mixed with an inert solid diluent, forexample calcium carbonate, calcium phosphate or kaolin, or as softgelatin capsules wherein the active ingredient is mixed with water or anoil medium, such as peanut oil, liquid paraffin or olive oil. Aqueoussuspensions can contain the chromium complex of the embodiments inadmixture with excipients suitable for the manufacture of aqueoussuspensions. Such excipients include suspending agents, dispersing orwetting agents, one or more preservatives, one or more coloring agents,one or more flavoring agents and one or more sweetening agents such assucrose or saccharin.

Oil suspensions can be formulated by suspending the active ingredient ina vegetable oil, such as arachis oil, olive oil, sesame oil or coconutoil, or in a mineral oil such as liquid paraffin. The oil suspension cancontain a thickening agent, such as beeswax, hard paraffin or cetylalcohol. Sweetening agents, such as those set forth above, and flavoringagents can be added to provide a palatable oral preparation. Thesecompositions can be preserved by an added antioxidant such as ascorbicacid. Dispersible powders and granules of the embodiments suitable forpreparation of an aqueous suspension by the addition of water providethe active ingredient in admixture with a dispersing or wetting agent, asuspending agent, and one or more preservatives. Additional excipients,for example sweetening, flavoring and coloring agents, can also bepresent.

Syrups and elixirs can be formulated with sweetening agents, such asglycerol, sorbitol or sucrose. Such formulations can also contain ademulcent, a preservative, a flavoring or a coloring agent.

The preparations for parenteral administration can be in the form of asterile injectable preparation, such as a sterile injectable aqueous oroleaginous suspension. This suspension can be formulated according tomethods well known in the art using suitable dispersing or wettingagents and suspending agents. The sterile injectable preparation canalso be a sterile injectable solution or suspension in a non-toxicparenterally-acceptable diluent or solvent, such as a solution in1,3-butanediol. Suitable diluents include, for example, water, Ringer'ssolution and isotonic sodium chloride solution. In addition, sterilefixed oils can be employed conventionally as a solvent or suspendingmedium. For this purpose, any bland fixed oil can be employed includingsynthetic mono or diglycerides. In addition, fatty acids such as oleicacid can likewise be used in the preparation of injectable preparations.

The pharmaceutical compositions can also be in the form of oil-in-wateremulsions. The oily phase can be a vegetable oil, such as olive oil orarachis oil, a mineral oil such as liquid paraffin, or a mixturethereof. Suitable emulsifying agents include naturally-occurring gumssuch as gum acacia and gum tragacanth, naturally occurring phosphatides,such as soybean lecithin, esters or partial esters derived from fattyacids and hexitol anhydrides, such as sorbitan mono-oleate, andcondensation products of these partial esters with ethylene oxide, suchas polyoxyethylene sorbitan mono-oleate. The emulsions can also containsweetening and flavoring agents.

When administered to a mammal, e.g., to an animal for veterinary use orfor improvement of livestock, or to a human for therapeutic use, thecompositions are administered in isolated form or as the isolated formin a therapeutic composition. As used herein, “isolated” means that thecompositions are separated from other components of either (a) a naturalsource, such as a plant or cell or food, preferably bacterial culture,or (b) a synthetic organic chemical reaction mixture. Preferably, viaconventional techniques, the compositions are purified. As used herein,“purified” means that when isolated, the isolate contains at least 95%,preferably at least 98% of the composition.

In some embodiments, the compositions are provided to the subjectorally. In other embodiments, the compositions are provided by any otherconvenient route, for example, by intravenous infusion or bolusinjection, by absorption through epithelial or mucocutaneous linings(e.g., oral mucosa, rectal and intestinal mucosa, etc.) and can beadministered together with another biologically active agent.Administration can be systemic or local. Various delivery systems usefulin the methods include for example, encapsulation in liposomes,microparticles, microcapsules, capsules, etc., and can be used toadminister a compound of the embodiments. In certain embodiments, morethan one composition is administered to an individual.

Other modes of administration useful in the methods include but are notlimited to intradermal, intramuscular, intraperitoneal, intravenous,subcutaneous, intranasal, epidural, oral, sublingual, intranasal,intracerebral, intravaginal, transdermal, rectally, by inhalation, ortopically, particularly to the ears, nose, eyes, or skin. The preferredmode of administration is left to the discretion of the professional,and will depend in-part upon the site of the condition to be treated. Inmost instances, administration will result in the release of thecompositions into the bloodstream.

In specific embodiments, it can be desirable to administer one or morecompositions locally to the area in need of treatment. This can beachieved, for example, and not by way of limitation, by local infusionduring surgery, topical application, e.g., in conjunction with a wounddressing after surgery, by injection, by means of a catheter, by meansof a suppository, or by means of an implant, said implant being of aporous, non-porous, or gelatinous material, including membranes, such assialastic membranes, or fibers. In one embodiment, administration can beby direct injection at the site (or former site) of an atheroscleroticplaque tissue

Pulmonary administration can also be employed, e.g., by use of aninhaler or nebulizer, and formulation with an aerosolizing agent, or viaperfusion in a fluorocarbon or synthetic pulmonary surfactant. Incertain embodiments, the compositions can be formulated as asuppository, with traditional binders and vehicles such astriglycerides.

Preferably, the compositions are formulated with a pharmaceuticallyacceptable vehicle. As used herein, the term “pharmaceuticallyacceptable” means approved by a regulatory agency of the Federal or astate government or listed in the U.S. Pharmacopeia or other generallyrecognized pharmacopeia for use in animals, and more particularly inhumans. The term “vehicle” refers to a diluent, adjuvant, excipient, orcarrier with which a compound of the embodiments is administered. Suchpharmaceutical vehicles can be liquids, such as water and oils,including those of petroleum, animal, vegetable or synthetic origin,such as peanut oil, soybean oil, mineral oil, sesame oil and the like.The pharmaceutical vehicles can be saline, gum acacia, gelatin, starchpaste, talc, keratin, colloidal silica, urea, and the like. In addition,auxiliary, stabilizing, thickening, lubricating and coloring agents maybe used. When administered to a patient, the compositions of theembodiments and pharmaceutically acceptable vehicles are preferablysterile. Water is a preferred vehicle when the compositions of theembodiments are administered intravenously. Saline solutions and aqueousdextrose and glycerol solutions can also be employed as liquid vehicles,particularly for injectable solutions. Suitable pharmaceutical vehiclesalso include excipients such as starch, glucose, lactose, sucrose,gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerolmonostearate, talc, sodium chloride, dried skim milk, glycerol,propylene, glycol, water, ethanol and the like. The presentcompositions, if desired, can also contain minor amounts of wetting oremulsifying agents, or pH buffering agents.

The present compositions can take the form of solutions, suspensions,emulsion, tablets, pills, pellets, capsules, capsules containingliquids, powders, sustained-release formulations, suppositories,emulsions, aerosols, sprays, suspensions, or any other form suitable foruse.

In some embodiments, the compositions are formulated for oral delivery,for example in the form of tablets, lozenges, aqueous or oilysuspensions, granules, powders, emulsions, capsules, syrups, or elixirs.Compounds and compositions described herein for oral delivery can alsobe formulated in foods and food mixes. Orally administered compositionscan contain one or more optionally agents, for example, sweeteningagents such as fructose, aspartame or saccharin; flavoring agents suchas peppermint, oil of wintergreen, or cherry; coloring agents; andpreserving agents, to provide a pharmaceutically palatable preparation.Moreover, where in tablet or pill form, the compositions can be coatedto delay disintegration and absorption in the gastrointestinal tractthereby providing a sustained action over an extended period of time.Selectively permeable membranes surrounding an osmotically activedriving compound are also suitable for orally administered compounds andcompositions described herein. In these later platforms, fluid from theenvironment surrounding the capsule is imbibed by the driving compound,which swells to displace the agent or agent composition through anaperture. These delivery platforms can provide an essentially zero orderdelivery profile as opposed to the spiked profiles of immediate releaseformulations. A time delay material such as glycerol monostearate orglycerol stearate can also be used. Oral compositions can includestandard vehicles such as mannitol, lactose, starch, magnesium stearate,sodium saccharine, cellulose, magnesium carbonate, etc. Such vehiclesare preferably of pharmaceutical grade.

In some embodiments, the compositions described herein can be in theform of nutraceutical packs not limited to functional foods, beverages,bars, dietary supplements, capsules, powder form or gelatin form,pharmaceutical packs or kits comprising one or more containers filledwith one or more compositions of the embodiments. Optionally associatedwith such container(s) can be a notice in the form prescribed by agovernmental agency regulating the manufacture, use or sale ofpharmaceuticals or biological products, which notice reflects approvalby the agency of manufacture, use or sale for human administration. In acertain embodiment, the kit contains more than one compound describedherein. In another embodiment, the kit comprises a compound describedherein and another lipid-mediating compound, glycemic control andantihypertensive drugs, including but not limited to insulin, statin, athiazolidinedione, or a fibrate or dietary modifications.

The compositions can be assayed in vitro and in vivo, for the desiredtherapeutic or prophylactic activity, prior to use in humans. Forexample, in vitro assays can be used to determine whether administrationof a specific compound described herein or a combination of compositionsof the embodiments are preferred for lowering fatty acid synthesis. Thecompositions can also be demonstrated to be effective and safe usinganimal model systems.

Throughout the specification there are references to identifying asubject in need of administration of a composition of the embodiments.The term identification is not intended to be limiting and includes ineach instance a belief by the subject that the composition will benefitthe subject, self-identification, and identification by third partyusing various techniques. The identification may be of at least onecondition selected from the group consisting of: sarcopenia, muscleatrophy, muscle wasting, muscular dystrophy, insulin resistance,cardiovascular disease, progressive renal disease, end stage renaldisease, endothelial dysfunction, left ventricular hypertrophy, cardiachyperreactivity, dyslipidemia, hyperglycemia, enhanced renninangiotensin activity, aldosterone syndrome, impaired pressurenatriuresis, chronic low grade inflammation, diabetes mellitus,hypertension, atherosclerosis, micoralbuminuria, obesity, depression,Syndrome X, polycystic ovary syndrome, cancer cachexia, spinal injuries,and combinations of any of the foregoing. The identification may beselection of a particular patient population, for example, elderlypatients, bed-ridden patients, and/or patients with low-protein diets.The identification may comprise identifying an individual that is takinga composition comprising a compound selected from the group consistingof: steroids, non-steroidal anti-inflammatory compounds, oralcontraceptives, implantable steroid contraceptives, hormone replacementtherapy, beta blockers, potassium channel openers, immunosuppressivedrugs, weight gainer formulations, human growth hormone, testosterone,and combinations thereof. Identification may also include analyzing apatient's family history and/or genetic profile.

In some embodiments, the subject may be elderly, bed-ridden, have alow-protein diet, and/or has one or more of sarcopenia, muscle atrophy,muscle wasting, muscular dystrophy, insulin resistance, cardiovasculardisease, progressive renal disease, end stage renal disease, endothelialdysfunction, left ventricular hypertrophy, cardiac hyperreactivity,dyslipidemia, hyperglycemia, enhanced rennin angiotensin activity,aldosterone syndrome, impaired pressure natriuresis, chronic low gradeinflammation, diabetes mellitus, hypertension, atherosclerosis,micoralbuminuria, obesity, depression, Syndrome X, polycystic ovarysyndrome, cancer cachexia, spinal injuries, and combinations of any ofthe foregoing. In some embodiments the subject is elderly. In someembodiments, the subject has progressive renal disease or end stagerenal disease. In some embodiments, the subject has sarcopenia.

As used herein, the term “treatment” or “treating” refers to anamelioration of a disease or disorder, or at least one discerniblesymptom thereof. The term “treatment” or “treating” refers to inhibitingthe progression of a disease or disorder, either physically, e.g.,stabilization of a discernible symptom, or physiologically, e.g.,stabilization of a physical parameter, or both.

In certain embodiments, the compositions are provided to a subject, suchas a mammal, as a preventative measure against such diseases. As usedherein, “prevention” or “preventing” refers to a reduction of the riskof acquiring a given disease or disorder alone or in combination withother clinical condition.

The combination chromium supplementation is useful for the methods fortreating obesity and related pathologies, obesity related tocomplications such as diabetes, diabetes risk factors, leptinresistance, abdominal fat distribution, cardiovascular disease and itsrelated pathologies, cardiovascular and related diseases, such as, forexample, hypertrophy, hypertension, congestive heart failure, myocardialischemia, ischemia reperfusion injuries in an organ, arrhythmia,myocardial infarction, and combinations of any of the foregoing. Oneembodiment is directed to a method of treating obesity and itsassociated complications such as diabetes, cardiovascular disease andinsulin resistance in a mammal by concurrently administering to themammal a therapeutically effective amount of a combination chromiumsupplementation and at least one starch.

The present invention is further disclosed in the following Examples,which are provided for illustrative purposes and are not in any wayintended to limit the scope of the invention as claimed.

EXAMPLES

Exemplary Procedures

Double-blind, cross-over design, with twenty subjects (10 men and 10women), between 22 and 65 are pre-screened using health historyquestionnaires, vital signs, and blood work. Participants must meet allof the following inclusion criteria in order to participate in thestudy: Provided voluntary signed and dated informed consent; were ingood health as determined by medical history and routine bloodchemistries; ages between 22 and 65 (inclusive) years; Body Mass Indexof 18.0-29.9 kg/m²; resting systolic blood pressure<140 mm Hg anddiastolic blood pressure<90 mm Hg during rested, seated measurements;normal resting heart rate of <90 per minute during rested, seatedmeasurements.

Participants with any of the conditions below are excluded from thestudy: history of diabetes; history of smoking; history of malignancy inthe previous 6 months; prior gastrointestinal bypass surgery (Lapband,etc.); chronic inflammatory condition or disease (Lupus, HIV/AIDS,etc.); known sensitivity or allergy to whey protein or chromium oramylopectin; subjects who currently use, and cannot refrain from usingchromium supplements; cannot refrain from consuming protein or aminoacid supplements during their participation in this study; will notrefrain from resistance training (outside any prescribed training)during the study period; currently participating in another researchstudy with an investigational product; hemoglobin less than 9.5 mg/dl atthe screening visit; concomitant use of corticosteroids or testosteronereplacement therapy (ingestion, injection, or transdermal), or use ofany other anabolic steroid; any other diseases or conditions that wouldplace the subject at increased risk of harm if they were to participate,at the discretion of the medical staff; cannot participate in anyresistance training activities more than 2 days per week.

All subjects are provided a particular diet, and asked to maintain theircurrent dietary habits. Each subject's baseline diet is analyzed viaNutriBase IX (Clinical Edition) to determine its energy andmacronutrient content. Before reporting to the laboratory for subsequenttesting, subjects will refrain from exercise for 72 hours, and fastedfor at least 8 hours prior to testing.

In addition to the prescribed diet and/or exercise regimen, subjects inthe test group are administered a supplement containing chromiumpicolinate, chromium histidinate, amylopectin, and 10 grams of wheyprotein. Subjects in the control group are administered a supplementwith only amylopectin and 10 grams of whey protein.

Example 1

In the presence of adequate whole protein and/or essential amino acids(EAA), insulin has a stimulatory effect on muscle protein synthesis,whereas in conditions of lower blood EAA concentrations, insulin has aninhibitory effect on protein breakdown. We determined the effect ofCrPic/CrHis+amylopectin (CAP) on changes in plasma concentrations ofEAA, insulin, and the fractional rate of muscle protein synthesis (FSR).Using a double-blind, cross-over design, ten subjects (6 men, 4 women)consumed 6 g whey protein+2 g of CrPic/CrHis+amylopectin (WCAP) or 6 gwhey protein (WP) after an overnight fast. FSR was measured using aprimed, continuous infusion of ring-d5-phenylalanine with serial musclebiopsies performed at 2, 4, and 8 hr. Plasma EAA and insulin wereassayed by ion-exchange chromatography and ELISA, respectively. Afterthe biopsy at 4 hr, subjects ingested their respective supplement,completed 8 sets of bilateral isotonic leg extension @ 80% of theirestimated 1-RM, and a final biopsy was obtained 4 hours later. Bothtrials increased EAA similarly, with peak levels noted 30 min afteringestion. Insulin tended (P=0.09) to be higher in the WCAP trial. FSRvalues increased by 32% in WCAP (+0.026%/hr, P<0.001 utilizing eitherthe plasma or intracellular precursor enrichment) and 21% afteringestion of WP (+0.012%/hr, P=NS), respectively. These data indicatethat the addition of CrPic/CrHis+amylopectin to a 6 g dose of wheyprotein increases FSR.

This was an open-label, single dose trial. Ten apparently healthysubjects (men/women=6/4), pre-screened using health historyquestionnaires, vital signs, and blood work were enrolled in the study.Completed subjects were between the ages of 22 and 34 years old.Research procedures included venous blood draws and vastus lateralismuscle biopsies during a primed, constant infusion ofL-[ring-d5]-phenylalanine. The fractional rate of muscle proteinsynthesis (FSR) was measured using the stable isotope tracerincorporation technique from vastus lateralis muscle biopsies performed2, 4, and 8 hrs after initiating stable isotope tracer infusion. Bloodsamples were collected at baseline (time 0) and at specified time pointsafter the beginning of stable isotope tracer infusion (i.e. +30 min, +1hr, +4 hr, and +8 hr) to assess changes in amino acid concentrations.After the biopsy at 4 hr, a single dose of WCAP was administered orallyand a final biopsy was obtained 4 hours later (i.e. 4 hourspost-prandial).

Participants met all of the following inclusion criteria in order toparticipate in the study: Provided voluntary signed and dated informedconsent; were in good health as determined by medical history androutine blood chemistries; ages between 21 and 45 (inclusive) years;Body Mass Index of 18.5-29.9 kg/m²; normotensive (resting systolic bloodpressure<140 mm Hg and diastolic blood pressure<90 mm Hg) during rested,seated measurements; normal resting heart rate (<90 per minute) duringrested, seated measurements.

Participants with any of the conditions below were excluded from thestudy: history of diabetes; history of smoking; history of malignancy inthe previous 6 months; prior gastrointestinal bypass surgery (Lapband,etc.); chronic inflammatory condition or disease (Lupus, HIV/AIDS,etc.); known sensitivity or allergy to whey protein or chromium oramylopectin; subjects who currently use, and cannot refrain from usingchromium supplements, or any other dietary ingredient that in theopinion of the research team might affect insulin sensitivity or glucosetolerance; do not or will not refrain from eating animal proteins duringtheir participation in this study; cannot refrain from consuming proteinor amino acid supplements during their participation in this study; willnot refrain from resistance training during the study period; currentlyparticipating in another research study with an investigational product;hemoglobin less than 9.5 mg/dl at the screening visit; concomitant useof corticosteroids or testosterone replacement therapy (ingestion,injection, or transdermal); any other diseases or conditions that wouldplace the subject at increased risk of harm if they were to participate,at the discretion of the medical staff; cannot participate in anyresistance training activities more than 2 days per week.

All subjects were asked to maintain their current dietary habits. Eachsubject's baseline diet was assessed by a 24-hour diet record, and wasanalyzed via NutriBase IX (Clinical Edition) to determine its energy andmacronutrient content (see Table 1 below). Before reporting to thelaboratory for subsequent testing, subjects followed their previouslyrecorded 24-hour diet records, refrained from exercise for 72 hours, andfasted for at least 8 hours prior to testing.

TABLE 1 Dietary intake of subjects (N = 10) at baseline. Subject TotalCHO FAT PRO CHO FAT PRO #/Gender Calories (g) (g) (g) (%) (%) (%) 01/M2641 165 102 264 25 35 40 02/M 2067 263 32 180 51 14 35 03/F 1905 185 80109 39 38 23 04/M 1873 234 49 121 50 24 26 05/M 2839 227 97 262 32 31 3706/M 3104 279 106 256 36 31 33 07/M 2312 213 97 144 37 38 25 08/F 1399139 46 104 42 30 28 09/F 1730 202 56 108 46 29 25 10/F 1326 198 22 82 6015 25Determination of Muscle Protein Synthesis

Subject Preparation: On the morning of the study and after an overnightfast (8 hrs), an 18-22 gauge polyethylene catheter was inserted intoeach arm; one was placed in a distal vein for heated blood sampling (5ml each time point), and another was placed in the forearm for infusionof the stable isotope tracers.

Amino Acid (Isotopic) Tracer: After insertion of peripheral catheters, aprimed (5.04 μmol/kg), constant (0.084 μmol/kg/min) infusion of thestable isotope (GRAS substance) ring-d₅-phenylalanine was started.Stable isotopes were obtained from Cambridge Isotope Laboratories(Tewksbury, MA) and tested for sterility and pyrogenicity (by CIL andthe preparing pharmacy—Cantrell Pharmacy). Prior to infusion, the stableisotope was then filtered during infusion through a sterile 0.22 micron(Millipore) filter placed in the infusion line.

Blood Sampling: Blood samples (5 ml) were collected in Lithium Heparintubes at baseline (time 0) and after the beginning of isotope infusion(4, 4+30, 5, 5+30, 6, 6+30, 7 and 8 hrs) for analysis of amino acidconcentrations, and for the analyses of plasma insulin and glucose (4,4+30, 5, 5+30, 6, 6+30 and 8 hrs). After centrifugation, plasma sampleswere stored in separate aliquots at −80 degrees C. until analysis.

Muscle Biopsy Procedure: Muscle biopsies from the vastus lateralis wereperformed after 2, 4, and 8 hrs of tracer infusion. After the biopsy at4 hr, a single dose of WCAP or the placebo was administered orally undersupervision. Muscle biopsies were performed under local anesthesia(using sterile 1% lidocaine, without epinephrine) for normal painmanagement and under strict sterile procedures. Prior to each musclebiopsy, a sterile field was created on the skin surface using a Betadineskin preparation kit. Then the skin and underlying tissue were injectedwith local anesthetic (Lidocaine) to minimize pain.

A 5 mm Bergstrom needle was advanced into the muscle through a small (˜1cm) incision produced by a #11 blade disposable scalpel. Immediatelyafter applying suction, a small sample of the muscle (approximately80-100 mg) was removed with the needle. The sample was cleaned withsterile saline, trimmed of any visible connective tissue, blotted, andthen cut into three equal portions. All three samples were immediatelyfrozen in liquid nitrogen and stored at −80° C.

After the biopsy procedure, the skin was cleansed, edges approximatedwith ¼ inch×1.5 inch adhesive Steri-strips, and a breathable filmdressing (Tegaderm) was applied to the site. Firm pressure wasmaintained until bleeding at the site ceased. To minimize the risk ofinfection and bruising, an antibiotic ointment and pressure dressing(with self-adhesive elastic bandage) were applied by the medical staffbefore the subject was released. All subjects were instructed to refrainfrom exercise for at least 48 hours and to use Tylenol for pain control,as needed.

After qualifying for the study, subjects were assigned to receive, indouble-blinded manner, whey protein (6 g) and 2.01 grams of the product(WCAP) or whey protein (6 g) and placebo. Whey supplements were preparedin powdered form, while product (WCAP) and placebo were prepared incapsule form. All supplements were packaged in coded generic containersfor double-blind administration.

The Supplement Fact Panel was used below

Chromium-Amylopectin Product

Supplement Facts Serving Size: 5 Capsules (2 grams) Servings PerContainer: 15 Amount % Daily Per Serving Value Chromium (from 1000 mcg834% Picolinate and Histidinate) Amylopectin (from waxy maize) 1790 mg †† Daily Value not established Other ingredients: Dicalcium phosphate,microcrystalline cellulose, gelatin, water, magnesium stearateSchematic Diagram of Visits

Test 2 Day Test (5-7 days 0 1 later) A. Informed Consent ✓ B. HealthHistory Questionnaire ✓ C. Physical Exam and EKG ✓ D. ComprehensiveBlood Chemistry * ✓ E. Vitals (HR and BP)** ✓ Height/Body Weight ✓ ✓ ✓Muscle Biopsies (3 per trial) ✓ ✓ Blood Amino Acid Analyses (9 timepoints) ✓ ✓ Phenylalanine Tracer Enrichment (8 time points) ✓ ✓Glucose/Insulin analyses (7 time points) ✓ ✓ Diet Record Analysis ✓ ✓Side Effect Questionnaire ✓ ✓ * includes: glucose, blood urea nitrogen,creatinine, AST, ALT, total bilirubin, alkaline phosphatase,triglycerides, cholesterol, HDL, LDL, sodium, potassium, total protein,albumin, globulin, iron, CBC, platelet count and differential white cellcount. **Enrollment of the subjects into a specific testing orderoccurred after the research staff cleared the questionnaires, vitals andblood work as being normal or within acceptable limits.

Compliance to product ingestion was confirmed by having all subjectsconsume their dose of WCAP in the presence of the medical staff.Compliance to diet and physical activity controls (i.e. 24-hr dietduplication, no exercise for 72 hours, 8-hr fast) was confirmed viaverbal acknowledgment by all subjects.

Outcome variables (muscle FSR and blood amino acid concentrations) wereanalyzed via dependent t-tests and one-way ANOVA, respectively, todetermine within-trial changes from baseline. Two-way factorial ANOVA(trial×time) was also employed to explore between-trial changes overtime. Statistical significance was set at P<0.05 and trends defined as0.051<P<0.10.

One female subject dropped out prior to the first biopsy due todizziness during the lidocaine injection procedure. She was promptlyreplaced with another female subject.

Six males and four females completed the study (see Table 1). Theaverage age, height, and weight of the subjects was: 26.6+/−3.7 years,175.5+/−10.9 centimeters (69.09 inches), and 78.56+/−17.4 kg (172.8lbs). Upon screening, normal values were obtained for blood pressure(122/78 mm Hg), heart rate (66 beats per minute), fasting blood sugar(93 mg/dL), fasting insulin (5 mIU/L), and HOMA-IR* (1.2) [*HOMA-IR=fasting insulin (μU/ml)/22.5*(glucose (mmol/l)); normal value<2in adults, <3 in children (Keskin et al., 2005)].

Consistent with previous investigations, a robust increase in plasmaessential amino acids (EAA) was realized after ingestion of WCAP (aswell as with placebo); with peaks levels achieved approximately 30 minpost-ingestion (i.e. occurring at 270 min on all graphs). EAAconcentrations returned to near baseline (fasted) levels approximately 3hr post-ingestion. Individual amino acids followed similar responses.Two-way ANOVA revealed no treatment by time interactions for any plasmaamino acid responses.

Muscle Fractional Synthesis Rate (FSR): The results indicate that theActive trial (i.e. WCAP) yielded a more robust response (≈32%) in FSRversus the Control trial (21%; P=0.001). Specifically, in the Activetrial, pre-treatment FSRpl was 0.0507±0.01% and post-treatment FSRpl was0.0745±0.016%. In the Control trial, pre-treatment FSRic was0.0532±0.023% while post-treatment FSRic was 0.0647±0.013%. Seeaccompanying graphs on page 20 and 21.

The significant response of the Active trial was achieved in light ofsimilar leucine and essential amino acid concentrations resultant fromeach treatment. A potential explanation for improved response of theActive trial may lie in its insulinogenic properties. Peak insulinresponse of the Active trial trended towards significance (p=0.09).

Data quality was quite satisfactory. Fasted and post-intervention FSRvalues, as well as their intra-subject variability, are reasonable andphysiological. Plasma leucine and EAA responses are also representativeof 6 grams of quality protein ingestion. Blood insulin indicated ageneral response to protein ingestion, though the potential differencenoted in the Active trial might be attributable to an ingredientparticular to this treatment. There was a small issue with subject 6during the Active trial. Despite repeated analyses and sampleprocessing, a reliable protein-bound enrichment of biopsy 1 was notattainable. The protein-bound enrichments of muscles 2 and 3 for thissubject X treatment were commensurate with the group data set, and thecalculated FSR for the post-intervention period was similar to the groupmean. These data indicate that study conduct was consistent and notresponsible for this anomalous finding. Upon questioning the subject, headmitted to dietary non-compliance during the Active trial. For thisreason, the ANOVA was performed with 10 subjects the Control trial and 9in the Active trial. If/when published, it is suggested that thisexplanation accompany the data/results description.

Potential side effects commonly associated with the consumption ofprotein/amino acids can include mild gastrointestinal disturbances(burping, nausea, etc.) as well as heartburn/acid reflux and flatulence.No such effects were noted in this study, nor were there changes inresting vital signs (i.e. heart rate and blood pressure) during thecourse of the study. Details of the subjects' responses to a SymptomQuestionnaire are provided in Table 2 and information on adverse eventsis detailed in Table 3.

TABLE 2 Symptom Questionnaire Responses Subject # - 01 02 03 04 05 06 0708 09 10 Trial A/B A/B A/B A/B A/B A/B A/B A/B A/B A/B Questions: Didyou have any NO NO NO NO NO NO NO NO NO NO difficulty adhering to thesupplementation protocol? Did you notice NO NO NO NO NO NO NO NO NO NOanything different with any of the following? a. your training outsidethe study; b. appetite; c. thirst; d. skin; e. upset stomach; f.diarrhea; g. gas or flatulence; h. headache; i. sex drive; j.sleepiness; k. nervousness or clarity of thought; l. aggression; m.muscle cramping; n. other

TABLE 3 Adverse Event Reporting Subject 01 02 03 04 05 06 07 08 09 10*D/O #1 Adverse Event NO NO yes NO NO NO YES (yes/no) Details of adverseevent (if yes) Event Numbness/ dizziness swelling Onset date Apr. 13,2015 Apr. 2, 2015 Onset time 8:00 am 10:30 am Resolve date Apr. 17, 2015Apr. 2, 2015 Resolve time 8:00 am 11:00 am Continuing at No NO end ofstudy (yes/no) Intensity 1 1 (1: mild 2: moderate 3: severe)Relationship 2 1 to study treatment (1: not related 2: unlikely 3:possibly 4: probably 5: definite) Treatment action 5 4 taken ice and (1:none massage 2: medication 3: hospitalization 4: discontinuation 5:other) Relationship to No NO study product Serious No NO *D/O = drop out

In summary, these data are consistent with a within-group effect for theActive trial increasing the muscle FSR response, whereas the Controltrial did not demonstrate such a within group effect by 1-way ANOVA. Aninterim power analysis, utilizing the data obtained thus far suggeststhat a total sample size of 14-17 subjects would provide 80% power fordetecting a significant difference (if one exists) for thiswithin-subject, 2-trial crossover design. Our recommendation would befor an additional 5 subjects enrolled if the goal is to show asignificant, comparative difference between treatments. Future effortsshould be directed towards a more chronic administration of WCAP onchanges in clinical endpoints (i.e., loss/gain of lean mass, functionaloutcomes, adaptations to structured exercise, etc.). Further, relativelysmall dose burden of the investigational product lends itself to testingwith a broad range of products and delivery systems in circumstanceswhere the anabolic response of skeletal muscle is desired.

Example 2

Example 2 is conducting using the general procedures described herein.DOMS: Using a comparison model with 2 independent variables (control andWCAP) and 6 dependent variables (maximal isometric and isokineticvoluntary strength, range of motion, upper arm circumference, plasmacreatine kinase activity, and muscle soreness). A 2-wayrepeated-measures analysis of variance and paired t-tests are used toexamine differences in changes of the dependent variable over time(before, immediately and 30 minutes after exercise, and 1, 2, 3, 4, 7,10, and 14 days post-exercise) between control and WCAP conditions.

Twenty healthy subjects (10 men and 10 women) with no history of upperarm injury and no experience in resistance training. In the single-blindstudy, the subjects are separated into control and WCAP groups, and eachsubject performs 10 sets of 6 maximal isokinetic (90°·s−1) eccentricactions of the elbow flexors with each arm on a dynamometer, separatedby 2 weeks. The control group receives a combination of whey protein andamylopectin (control), while the WCAP group receives a combination ofwhey protein and amylopectin with chromium histidinate and chromiumpicolinate. The two combinations are iso-volumic and are equivalent inprotein and carbohydrate content.

Maximal voluntary isometric and isokinetic elbow flexor strength, rangeof motion, upper arm circumference, plasma creatine kinase activity, andmuscle soreness are measured. Delayed-onset muscle soreness issignificantly less for the WCAP group for peak soreness in extending theelbow joint and palpating the brachioradialis muscle. Soreness whileflexing the elbow joint and palpating the brachialis muscle is also lessin the WCAP group. WCAP has significant effects on plasma creatinekinase activity, with a lower peak value at 4 days post-exercise, andupper arm circumference, with a smaller increase than the control at 3and 4 days post-exercise. Significant effects of WCAP on recovery ofmuscle strength is also evident. WCAP is also effective in alleviatingDOMS, and reducing post-exercise muscle swelling, and recovering musclefunction.

Example 3

Aerobic Exercise Recovery: Nine male, endurance-trained cyclists performan interval workout followed by 4 hr. of recovery, and a subsequentendurance trial to exhaustion at 70% VO₂ max, on three separate days.

Immediately following the first exercise bout and 2 hr. of recovery,subjects drink iso-volumic amounts of WCAP, protein and fluidreplacement drink (FR), or carbohydrate replacement drink (CR), in asingle-blind, randomized design. Carbohydrate content is equivalent forWCAP and CR and protein content is equivalent for WCAP and FR. Time toexhaustion (TTE), average heart rate (HR), rating of perceived exertion(RPE), and total work (WT) for the endurance exercise were comparedbetween trials. TTE and WT are significantly greater for the WCAP groupcompared to the FR and CR groups. This suggests that WCAP is aneffective recovery aid between two exhausting aerobic exercise bouts,and that WCAP increases exercise stamina.

Example 4

Recovery from Resistance Exercise: WCAP supplementation maintains ashort-term net anabolic hormonal profile and decreases muscle celldamage during periods of high-intensity resistance training(overreaching), thereby enhancing recovery and decreasing the risk ofinjury and illness.

Twenty previously resistance trained males are randomly assigned toeither a WCAP or placebo group (receiving an equal amount of wheyprotein and amylopectin as the WCAP group). Subjects consume thesupplement for 3 weeks before commencing a fourth week ofsupplementation with concomitant high-intensity total-body resistancetraining (overreaching) (3 3 6-8 repetitions maximum, 8 exercises).Blood is drawn prior to and after supplementation, then again after 2and 4 days of training. Serum is analyzed for testosterone, cortisol,and creatine kinase. Serum testosterone levels are significantly higher,and cortisol and creatine kinase levels are significantly lower in theWCAP group during and following resistance training.

This suggests that WCAP supplementation produces a net anabolic hormonalprofile while attenuating training-induced increases in muscle tissuedamage. Athletes' nutrient intake, which periodically increases aminoacid intake to reflect the increased need for recovery during periods ofoverreaching, may increase subsequent competitive performance whiledecreasing the risk of injury or illness.

Example 5

Increasing Muscle Mass: Using a protocol, similar to that describedabove, subjects are instructed to follow a diet and exercise regimen for4 weeks, including resistance training three days per week. At thecompletion of the study, subjects' body mass and body fat percentage aremeasured. The test group shows an average of about 5% more muscle massthan the control group.

Example 6

Increasing the Rate of Muscle Hypertrophy: Using the standard protocol,described above, subjects are instructed to follow a diet and exerciseregimen for 4 weeks, including resistance training three days per week.At the completion of the study, the circumference of subjects' biceps,quadriceps, and chest are measured. The test group shows an averageincrease in circumference of about 5% relative to the control group.

Example 7

Increasing the Muscle Uptake of Branched Chain Amino Acids: Using thestandard protocol, described above, subjects are instructed to follow adiet and exercise regimen for 4 weeks, including resistance trainingthree days per week. Once each week, a muscle biopsy is obtained(according to the procedure described in Example 1), one hour afteradministration of the supplement. One biopsy is obtained from each armand leg, for a total of four biopsies over the four week trial. The testgroup shows an average increase in cellular levels of branched chainamino acids (leucine, isoleucine, and valine) of about 15% relative tothe control group.

Example 8

Decreasing Muscle Soreness: Using the standard protocol, describedabove, subjects are instructed to follow a diet and exercise regimen for4 weeks, including resistance training three days per week. However, thesubjects in this trial also self-identify as exercise naiver (e.g., 0 to1 bouts of intense exercise and/or resistance training per week).Subjects fill out a questionnaire regarding their soreness level priorto beginning the trial, and then each day throughout the trial. The testgroup reports 25% less soreness relative to the control group.

Example 9

Process for Making Chromium, Starch, and Protein Compositions: Theprotein source(s) and the starch(es) are mixed in water to form a wetblend. The wet blend is then spray dried, followed by dry mixing withchromium picolinate and chromium histidinate. In an alternative processthe ingredients are simply dry blended.

Example 10

The subject rats were divided into nine groups: Exercise alone, 0.465grams whey protein per kilogram of body weight (g/kg), 1.55 g/kg wheyprotein, 2.33 g/kg whey protein, 3.1 g/kg whey protein, 0.465 g/kg WCAP,1.55 g/kg WCAP, 2.33 g/kg WCAP, and 3.1 g/kg WCAP. The dose of protein,using human doses converted to rate using a conversion factor to rat of6.2, provides the following: 0.465 grams in the study is equivalent to ahuman dose of 6 grams; 1.55 g is equivalent to 20 grams; 2.33 g isequivalent to 20 grams; and 3.1 g is equivalent to 40 grams. See Nairand Jacob, J. Basic Clin. Pharm., Vol. 7, No. 2, pp. 27-31 (2016).

The results demonstrate a ceiling of FSR at a dose of 2.33 g/kg ofprotein alone (FIG. 18 ). Administration of WCAP provided anunexpectedly significant increase in FSR even at protein levels over themaximum FSR achieved with protein alone (FIG. 18 ). Thus, ingestion ofprotein as WCAP provides FSR levels greater than the maximum FSR levelsobserved with protein alone (FIG. 19 , vertical arrow). Likewise, theFSR of lower doses of WCAP were also unexpectedly enhanced,demonstrating equivalent FSR to levels achieved with substantiallyhigher doses of protein alone (FIG. 18 ). For example, 0.465 g/kg WCAPincreased FSR up to levels observed with 1.55 g/kg of whey proteinalone. Accordingly, ingestion of 0.465 g/kg WCAP provides an equivalentFSR to ingestion of 3.33-fold more protein alone. Surprisingly,significantly less total protein intake (as WCAP) is required to achieveequivalent FSR rates compared to protein alone (FIG. 19 , horizontalarrow).

The methods, compositions, and devices described herein are presentlyrepresentative of preferred embodiments and are exemplary and are notintended as limitations on the scope of the invention. Changes thereinand other uses will occur to those skilled in the art which areencompassed within the spirit of the invention and are defined by thescope of the disclosure. Accordingly, it will be apparent to one skilledin the art that varying substitutions and modifications can be made tothe invention disclosed herein without departing from the scope andspirit of the invention.

While the disclosure has been illustrated and described in detail in thedrawings and foregoing description, such illustration and descriptionare to be considered illustrative or exemplary and not restrictive. Thedisclosure is not limited to the disclosed embodiments. Variations tothe disclosed embodiments can be understood and effected by thoseskilled in the art in practicing the claimed disclosure, from a study ofthe drawings, the disclosure and the appended claims.

Unless otherwise defined, all terms (including technical and scientificterms) are to be given their ordinary and customary meaning to a personof ordinary skill in the art, and are not to be limited to a special orcustomized meaning unless expressly so defined herein. It should benoted that the use of particular terminology when describing certainfeatures or aspects of the disclosure should not be taken to imply thatthe terminology is being re-defined herein to be restricted to includeany specific characteristics of the features or aspects of thedisclosure with which that terminology is associated. Terms and phrasesused in this application, and variations thereof, especially in theappended claims, unless otherwise expressly stated, should be construedas open ended as opposed to limiting. As examples of the foregoing, theterm ‘including’ should be read to mean ‘including, without limitation,’including but not limited to,' or the like; the term ‘comprising’ asused herein is synonymous with ‘including,’ containing,' or‘characterized by,’ and is inclusive or open-ended and does not excludeadditional, unrecited elements or method steps; the term ‘having’ shouldbe interpreted as ‘having at least;’ the term ‘includes’ should beinterpreted as ‘includes but is not limited to;’ the term ‘example’ isused to provide exemplary instances of the item in discussion, not anexhaustive or limiting list thereof; adjectives such as ‘known’,‘normal’, ‘standard’, and terms of similar meaning should not beconstrued as limiting the item described to a given time period or to anitem available as of a given time, but instead should be read toencompass known, normal, or standard technologies that may be availableor known now or at any time in the future; and use of terms like‘preferably,’ ‘preferred,’ ‘desired,’ or ‘desirable,’ and words ofsimilar meaning should not be understood as implying that certainfeatures are critical, essential, or even important to the structure orfunction of the invention, but instead as merely intended to highlightalternative or additional features that may or may not be utilized in aparticular embodiment of the invention. Likewise, a group of itemslinked with the conjunction ‘and’ should not be read as requiring thateach and every one of those items be present in the grouping, but rathershould be read as ‘and/or’ unless expressly stated otherwise. Similarly,a group of items linked with the conjunction ‘or’ should not be read asrequiring mutual exclusivity among that group, but rather should be readas ‘and/or’ unless expressly stated otherwise.

As used in the claims below and throughout this disclosure, by thephrase “consisting essentially of” is meant including any elementslisted after the phrase, and limited to other elements that do notinterfere with or contribute to the activity or action specified in thedisclosure for the listed elements. Thus, the phrase “consistingessentially of” indicates that the listed elements are required ormandatory, but that other elements are optional and may or may not bepresent depending upon whether or not they affect the activity or actionof the listed elements.

Where a range of values is provided, it is understood that the upper andlower limit, and each intervening value between the upper and lowerlimit of the range is encompassed within the embodiments.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity. The indefinite article “a” or “an” does not exclude aplurality. A single processor or other unit may fulfill the functions ofseveral items recited in the claims. The mere fact that certain measuresare recited in mutually different dependent claims does not indicatethat a combination of these measures cannot be used to advantage. Anyreference signs in the claims should not be construed as limiting thescope.

It will be further understood by those within the art that if a specificnumber of an introduced claim recitation is intended, such an intentwill be explicitly recited in the claim, and in the absence of suchrecitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to embodiments containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that virtually any disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms. For example, the phrase “A or B” will be understood toinclude the possibilities of “A” or “B” or “A and B.”

All numbers expressing quantities of ingredients, reaction conditions,and so forth used in the specification are to be understood as beingmodified in all instances by the term ‘about.’ Accordingly, unlessindicated to the contrary, the numerical parameters set forth herein areapproximations that may vary depending upon the desired propertiessought to be obtained. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of anyclaims in any application claiming priority to the present application,each numerical parameter should be construed in light of the number ofsignificant digits and ordinary rounding approaches.

Furthermore, although the foregoing has been described in some detail byway of illustrations and examples for purposes of clarity andunderstanding, it is apparent to those skilled in the art that certainchanges and modifications may be practiced. Therefore, the descriptionand examples should not be construed as limiting the scope of theinvention to the specific embodiments and examples described herein, butrather to also cover all modification and alternatives coming with thetrue scope and spirit of the invention.

What is claimed is:
 1. A nutritional supplement comprising: chromiumpicolinate (CrPic), chromium histidinate (CrHis); and a saccharide;wherein the CrPic, CrHis, and the saccharide are present in an amounteffective to increase muscle mass in a human subject.
 2. The nutritionalsupplement of claim 1, wherein the total amount of CrPic and CrHis isbetween about 0.001% (w/w) and about 3% (w/w).
 3. The nutritionalsupplement of claim 1, wherein the supplement is a powder.
 4. Thenutritional supplement of claim 1, wherein the supplement is a liquid.5. The nutritional supplement of claim 1, wherein the saccharidecomprises amylopectin.
 6. The nutritional supplement of claim 1, whereinthe nutritional supplement consists essentially of chromium picolinate,chromium histidinate, and a saccharide.
 7. The nutritional supplement ofclaim 1, further comprising a compound selected from the groupconsisting of caffeine, creatine, creatine hydrochloride, creatinemonohydrate, taurine, guarana, vitamin C, vitamin B₁, vitamin B₂,vitamin B₃, vitamin B₅, vitamin B₆, vitamin B₇, vitamin B₉, and vitaminB₁₂, or a combination thereof.
 8. The nutritional supplement of claim 5,wherein the weight ratio of CrHis and CrPic, combined, to the saccharideis from about 1:1 to about 1:2000.
 9. The nutritional supplement ofclaim 1, wherein the nutritional supplement comprises between about 100mcg and about 2,000 mcg of CrPic and CrHis, combined.
 10. Thenutritional supplement of claim 1, wherein the nutritional supplementcomprises between about 50 mcg and about 1,500 mcg of CrHis and CrPic,combined.
 11. The nutritional supplement of claim 5, wherein thenutritional supplement comprises between about 100 mg and about 3,000 mgof the saccharide.
 12. The nutritional supplement of claim 5, whereinthe saccharide is derived from waxy maize.